Preparation of Hydroxyapatite-Alginate Gels as a Carrier for Controlled Release of Paclitaxel

Abstract:

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Hydroxyapatite (HAp)-alginate gels were developed as drug delivery carriers of the
anti-cancer drug, water-insoluble paclitaxel (Taxol). The spray-drying technique was employed for
loading the paclitaxel into spherical HAp microparticles with 1 to 20 μm in diameter. The
microparticles loaded with 2.4 or 7.3wt% of paclitaxel were then mixed with sodium alginate,
which was followed by Ca2+-mediated gelation. The compressive strength of the HAp-alginate gels
and the release of paclitaxel from the gels in a medium were investigated in vitro. The alginate
matrix was effective for the achievement of controlled release of anti-cancer drugs.

Abstract: The extent of osseous involvement, particularly spinal cord compression, is directly
correlated with patient survival. To treat metastatic spine cancer, we have developed novel
paclitaxel-loaded hydroxyapatite-alginate gels. In this study, an intraosseous spinal cancer model in
rats was used to investigate the efficacy of local treatment. Ten rats were randomized into two groups,
a local treatment group and a control group. Disease-free time and survival rate in the local treatment
group were significantly longer in this model. (p<0.05)

Abstract: Rigid hydroxyapatite (HAp)-alginate beads were prepared as drug delivery carriers for an
anti-cancer drug, paclitaxel (Taxol). Paclitaxel was loaded into the HAp microparticle in process of a
spray-drying technique. The HAp-alginate beads including paclitaxel were obtained by a droplet
method into barium solution as ionic cross-linkage and dehydration. Cross-sectional analyses
indicated the homogeneity of HAp microparticles and barium ions inside the bead. The ratio of
alginate to HAp in the beads dominated both mechanical and swelling properties. Drug-release
experiment demonstrated the sustained release of paclitaxel from the beads cross-linked with barium
ion for 7 days.

Abstract: Several drug delivery carriers have reported on local delivery of paclitaxel (PTX), but their effects on intraosseous cancer model are not well known. This study was conducted to clarify the therapeutic effects of our newly developed PTX-loaded HAp-alginate composite beads. Cytotoxic activity was assessed on rat’s mammary adenocarcinoma by cell proliferation assay using WST-1 reagent. Antitumor activity was assessed by 8-week-old rat female Fischer 344 rats of metastatic spine cancer. Twenty-three rats were divided into 3 groups: Group 1 (n = 7) and Group 2 (n = 8) was treated with the PTX-loaded HAp-alginate beads using strontium ions and barium ions, respectively. Group 3 (n = 8) was administered with drug-free HAp-alginate beads. We checked disease-free time and survival time among 3 groups. The HAp-alginate beads containing 2.4wt% of PTX showed significant cytotoxic activity on CRL-1666 cells. The effects were decreased with time during 72 h. The animals treated with 2.4wt% of PTX-loaded HAp-alginate beads showed 40% increase in the disease-free time and 25% increase in survival time. Our studies suggest that newly developed HAp-alginate beads can be a candidate carrier of PTX to bone.

Abstract: Tea polyphenol loaded alginate-chitosan microspheres were prepared by ionic gelation method for controlling tea polyphenol release by using various combinations of chitosn and Ca2+ as cation and alginate as anion.Scanning electron microscopy were used to investigate the surface characteristics of tea polyphenol loaded microspheres. These microencapsulated beads were evaluated as a pH-sensitive system for delivery of tea polyphenol. The main advantage of this system is that all procedures used were performed in aqueous medium which may preserve the tea polyphenol bioactivity. At pH7.4, the amounts of tea polyphenol released increased significantly as compared to those released at pH1.2. It is evident that the rate of tea polyphenol release could be controlled by changing the chitosan and the calcium chloride concentrations.

Abstract: Temperature-sensitive calcium alginate-based microspheres were prepared in two steps. Firstly, free-radical polymerization of temperature-sensitive N-vinylcaprolactam monomer was performed in aqueous solution of sodium alginate, yielding a mixed aqueous solution bearing temperature-sensitivity composed of poly(N-vinylcaprolactam), sodium alginate-graft- poly(N-vinylcaprolactam) and sodium alginate. Then temperature-sensitive composite microspheres were prepared by inverse emulsification-crosslinking using the as-prepared solution as water phase, n-hexane as oil phase, Span-85 and Tween-85 as emulsifiers and calcium chloride as crosslinker respectively. The morphology and temperature-sensitivity of the composite microspheres were investigated by scanning electron microscope and turbidity method respectively. The controlled release behavior of the microspheres towards temperature was investigated preliminarily using berberine as a model drug.